The Experts below are selected from a list of 675 Experts worldwide ranked by ideXlab platform

Mila Sajinovic - One of the best experts on this subject based on the ideXlab platform.

  • A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas
    Cell Communication and Signaling, 2020
    Co-Authors: Monika Wimmer, Roland Zauner, Michael Ablinger, Josefina Piñón-hofbauer, Christina Guttmann-gruber, Manuela Reisenberger, Thomas Lettner, Norbert Niklas, Johannes Proell, Mila Sajinovic
    Abstract:

    Background Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined. Methods MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets. Results Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2. Conclusion The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA.

Malgorzata Wierzbicka - One of the best experts on this subject based on the ideXlab platform.

  • DIAPH2 alterations increase cellular motility and may contribute to the metastatic potential of laryngeal squamous cell carcinoma
    Carcinogenesis, 2019
    Co-Authors: Magdalena Kostrzewskapoczekaj, Ewa Byzia, Natalia Soloch, Malgorzata Jarmuzszymczak, Joanna Janiszewska, Ewelina Kowal, Julia Paczkowska, Katarzyna Kiwerska, Malgorzata Wierzbicka
    Abstract:

    Low 5-year survival rate in laryngeal squamous cell carcinoma (LSCC) is to large extent attributable to high rate of recurrences and metastases. Despite the importance of the latter process, its complex genetic background remains not fully understood. Recently, we identified two metastasis-related candidate genes, DIAPH2 and DIAPH3 to be frequently targeted by hemizygous/homozygous deletions, respectively, in LSCC cell lines. They physiologically regulate such processes as cell movement and adhesion, hence we found it as a rationale, to study if tumor LSCC specimens harbor mutations of these genes and whether the mutations are associated with metastasizing tumors. As a proof of concept, we sequenced both genes in five LSCC cell lines derived from lymph node metastases assuming there the highest probability of finding alterations. Indeed, we identified one hemizygous deletion (c.3116_3240del125) in DIAPH2 targeting the FH2 domain. Moreover, we analyzed 95 LSCC tumors (53 N0 and 42 N+) using the Illumina platform and identified three heterozygous single nucleotide variants in DIAPH2 targeting conserved domains exclusively in N+ tumors. By combining these results with cBioPortal data we showed significant enrichment of DIAPH2 mutations (P = 0.036) in N+ tumors. To demonstrate the consequences of DIAPH2 inactivation, CRISPR/Cas9 editing was used to obtain a heterozygous DIAPH2+/- mutant HEK-293T cell line. Importantly, the edited line shows a shift from 'proliferation' to 'migration' phenotype typically observed in metastasizing cells. In conclusion, we report that DIAPH2 alterations are present primarily in metastasizing specimens of LSCC and suggest that they may contribute to the metastatic potential of the tumor.

Monika Wimmer - One of the best experts on this subject based on the ideXlab platform.

  • A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas
    Cell Communication and Signaling, 2020
    Co-Authors: Monika Wimmer, Roland Zauner, Michael Ablinger, Josefina Piñón-hofbauer, Christina Guttmann-gruber, Manuela Reisenberger, Thomas Lettner, Norbert Niklas, Johannes Proell, Mila Sajinovic
    Abstract:

    Background Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined. Methods MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets. Results Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2. Conclusion The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA.

Malgorzata Jarmuzszymczak - One of the best experts on this subject based on the ideXlab platform.

  • DIAPH2 alterations increase cellular motility and may contribute to the metastatic potential of laryngeal squamous cell carcinoma
    Carcinogenesis, 2019
    Co-Authors: Magdalena Kostrzewskapoczekaj, Ewa Byzia, Natalia Soloch, Malgorzata Jarmuzszymczak, Joanna Janiszewska, Ewelina Kowal, Julia Paczkowska, Katarzyna Kiwerska, Malgorzata Wierzbicka
    Abstract:

    Low 5-year survival rate in laryngeal squamous cell carcinoma (LSCC) is to large extent attributable to high rate of recurrences and metastases. Despite the importance of the latter process, its complex genetic background remains not fully understood. Recently, we identified two metastasis-related candidate genes, DIAPH2 and DIAPH3 to be frequently targeted by hemizygous/homozygous deletions, respectively, in LSCC cell lines. They physiologically regulate such processes as cell movement and adhesion, hence we found it as a rationale, to study if tumor LSCC specimens harbor mutations of these genes and whether the mutations are associated with metastasizing tumors. As a proof of concept, we sequenced both genes in five LSCC cell lines derived from lymph node metastases assuming there the highest probability of finding alterations. Indeed, we identified one hemizygous deletion (c.3116_3240del125) in DIAPH2 targeting the FH2 domain. Moreover, we analyzed 95 LSCC tumors (53 N0 and 42 N+) using the Illumina platform and identified three heterozygous single nucleotide variants in DIAPH2 targeting conserved domains exclusively in N+ tumors. By combining these results with cBioPortal data we showed significant enrichment of DIAPH2 mutations (P = 0.036) in N+ tumors. To demonstrate the consequences of DIAPH2 inactivation, CRISPR/Cas9 editing was used to obtain a heterozygous DIAPH2+/- mutant HEK-293T cell line. Importantly, the edited line shows a shift from 'proliferation' to 'migration' phenotype typically observed in metastasizing cells. In conclusion, we report that DIAPH2 alterations are present primarily in metastasizing specimens of LSCC and suggest that they may contribute to the metastatic potential of the tumor.

Nam Keun Kim - One of the best experts on this subject based on the ideXlab platform.

  • Validation of POI-related miR-146aC>G target genes.
    2017
    Co-Authors: Sung Hwan Cho, Kyung Ah Kim, Ji Hyang Kim, Young Ran Kim, Eun Hee Ahn, Hyungchul Rah, Woo Sik Lee, Nam Keun Kim
    Abstract:

    Validation of the expression using qRT-PCR. Transient transfection of pGL4.13 plasmids with FOXO3, FOXl2, ESR1, BBS9, DIAPH2, and FOXE1 in the KGN cell line. mRNA expression levels were normalized to those of GAPDH expression. The data indicate the mean values with the standard deviation relative to miR-mimic negative expression from three independent experiments. Control (miR-scrambled + pGL4.13–3’UTR of target gene). *P

  • Expression of POI-related miR-146aC>G target genes.
    2017
    Co-Authors: Sung Hwan Cho, Kyung Ah Kim, Ji Hyang Kim, Young Ran Kim, Eun Hee Ahn, Hyungchul Rah, Woo Sik Lee, Nam Keun Kim
    Abstract:

    Validation of the expression of down-regulated genes from microarrays (A-F) and qPCR-arrays (G-L). Transient transfection of pGL4.13 plasmids with FOXO3, FOXl2, ESR1, BBS9, DIAPH2, and FOXE1 in the KGN cell line. mRNA expression levels were normalized to those of GAPDH expression. The data indicate the mean values with the standard deviation relative to miR-mimic negative expression from three independent experiments. Control (miR-scrambled + pGL4.13–3’UTR of each target gene). *P